Project description: The HIV envelope glycoprotein (Env) sequentially interacts with CD4 and coreceptor (either CCR5 or CXCR4) to initiate the fusion reaction between the viral envelope and the host membrane. The components of these reactions are of fundamental importance to the clinical HIV-1 field because they are the targets of broadly neutralising antibodies (bnAbs) that currently offer the best hope for vaccine development and infection prevention strategies. Little detail is known, however, about the molecular mechanisms by which the HIV-1 envelope spike (Env) influences CD4 and coreceptors and how this process culminates in fusion with the host cell membrane. Structural studies have provided the intramolecular basis for receptor-binding-induced conformational changes during HIV-1 Env priming. How these conformational rearrangements between HIV Env and CD4 and coreceptors lead to a particular receptor stoichiometry, and therefore the inter-molecular dynamics during the pre-fusion reaction in live cells, however, is not known.
This Ph.D studentship will study utilizing advanced single molecule light microscopy techniques which are the spatial and temporal mechanism/s for this reaction in the context of live cells (T Cells and macrophages). The Ph.D comprises the use of advanced molecular biology, cell culture, use of cutting edge light microscopes and data analysis.
Academic requirements: BSc and/or MSc in Biophysics, Biotechnology, Molecular Biology or Physics.
English language requirements: Band D (Please refer to King’s English language requirements).